Pharmacology & Mechanism
- Oral prodrug converted to abiraterone.
- Selective, irreversible CYP17A1 inhibitor → blocks 17α-hydroxylase & 17,20-lyase.
- Results in suppression of androgen biosynthesis in testes, adrenal glands, and tumor tissue.
- Androgen deprivation slows prostate cancer progression.
Indications
- Metastatic castration-sensitive prostate cancer (mCSPC) → with prednisone + ADT.
- Metastatic castration-resistant prostate cancer (mCRPC) → both pre- and post-docetaxel settings, with prednisone + ADT.
Dosing
- Standard (Zytiga®): 1000 mg PO once daily (four × 250 mg or two × 500 mg tablets) on an empty stomach.
- Yonsa® (micronized formulation): 500 mg PO once daily (four × 125 mg tablets), less food effect.
- Must be given with prednisone 5–10 mg daily (to suppress mineralocorticoid excess).
Toxicities & Monitoring
- Mineralocorticoid excess: hypertension, hypokalemia, fluid retention → monitor BP, electrolytes.
- Hepatotoxicity: monitor LFTs (baseline, every 2 weeks × 3 months, then monthly).
- CV risk: arrhythmias, heart failure (caution in cardiac disease).
- Other: fatigue, hot flashes, arthralgia.
Clinical Pearls for Pharmacists
- Prednisone required → mitigates mineralocorticoid side effects.
- Empty stomach administration → food ↑ exposure up to 10-fold (risk of severe toxicity).
- Continue ADT (GnRH agonist/antagonist or orchiectomy) alongside.
- Drug interactions: CYP3A4 substrate; strong inducers (e.g., rifampin) ↓ exposure; inhibits CYP2D6 and CYP2C8 (watch SSRIs, beta-blockers, antipsychotics).